Open Access. Powered by Scholars. Published by Universities.®
- Discipline
-
- Biochemistry (7)
- Biochemistry, Biophysics, and Structural Biology (7)
- Life Sciences (7)
- Molecular Biology (7)
- Genetic Structures (2)
-
- Analytical, Diagnostic and Therapeutic Techniques and Equipment (1)
- Chemical and Pharmacologic Phenomena (1)
- Chemicals and Drugs (1)
- Diseases (1)
- Enzymes and Coenzymes (1)
- Genetics and Genomics (1)
- Investigative Techniques (1)
- Medical Biochemistry (1)
- Medical Neurobiology (1)
- Medical Specialties (1)
- Neurology (1)
- Nucleic Acids, Nucleotides, and Nucleosides (1)
- Pathological Conditions, Signs and Symptoms (1)
- Systems Biology (1)
- Keyword
-
- Humans (4)
- Animals (3)
- Cell Line (2)
- Cell line (2)
- Drosophila melanogaster (2)
-
- Mitochondria (2)
- ABCC6 (1)
- ARS (1)
- Aging (1)
- Alternative end-joining (1)
- Alzheimer Disease (1)
- Aminoacyl-tRNA synthetase (1)
- Amyloid beta-Peptides (1)
- And sideroblastic anemia (1)
- Animal (1)
- Axons (1)
- Base editing (1)
- Behavior (1)
- Behavior, Animal (1)
- Brain (1)
- CRISPR (1)
- Calcium (1)
- Calcium Channels (1)
- Calcium channels (1)
- Cells (1)
- Cells, Cultured (1)
- Cold Spring Harbor (1)
- Cultured (1)
- Cyclic AMP (1)
- Cyclic AMP-Dependent Protein Kinases (1)
Articles 1 - 9 of 9
Full-Text Articles in Genetic Phenomena
Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt
Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt
Department of Biochemistry and Molecular Biology Faculty Papers
Mitochondrial DNA replication occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria (ERMCS). Beyond the known role of the tubular ER protein RTN4, the factors regulating this process are poorly defined. Here, we show that repressing the ER protein ERLIN2 in human fibroblasts depletes ER-mitochondrial contact sites and inhibits mitochondrial DNA replication, as does silencing RTN4 or the ER-mitochondrial tether GRP75. GRP75 or RTN4 scarcity also decreases the level of the mitochondrial calcium uniporter (MCU), whose inhibition blocks mitochondrial DNA synthesis. Because ERMCS depletion did not diminish mitochondrial calcium, and MCU complex can transport manganese, we tested whether …
Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik
Dna Extrusion Size Determines Pathway Choice During Cag Repeat Expansion, Mayuri Bhatia, Ashutosh S. Phadte, Anna Lakhina, Anthony R. Monte Carloi Iii, Sarah Barndt, Anna Pluciennik
Department of Biochemistry and Molecular Biology Faculty Papers
DNA triplet repeat expansion causes several primarly neurological disorders like Huntington's disease, myotonic dystrophy type 1, and fragile-X related disorders. There is general consensus that recognition of extrahelical extrusions or hairpin-loop structures (formed by strand slippage) by the DNA mismatch repair protein MutSβ leads to repeat expansion by a mutagenic process. By contrast, the FAN1 nuclease attenuates triplet repeat expansion, the molecular basis of which was explained by our recent finding that FAN1 nuclease cleaves and initiates removal of extrahelical extrusions. Here we show that extrusions containing two or more triplet repeats are subject to recognition and processing by either …
Liver-Directed Base Editing Of Abcc6 Prevents Ectopic Calcification In A Variant-Humanized Mouse Model Of Pseudoxanthoma Elasticum, Lauren C. Testa, Dora Obiri-Yeboah, Hooda Said, Ping Qu, Michael A. Levine, Mohamad-Gabriel Alameh, Kiran Musunuru, Qiaoli Li, Xiao Wang
Liver-Directed Base Editing Of Abcc6 Prevents Ectopic Calcification In A Variant-Humanized Mouse Model Of Pseudoxanthoma Elasticum, Lauren C. Testa, Dora Obiri-Yeboah, Hooda Said, Ping Qu, Michael A. Levine, Mohamad-Gabriel Alameh, Kiran Musunuru, Qiaoli Li, Xiao Wang
Department of Biochemistry and Molecular Biology Faculty Papers
Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective tissue disorder characterized by ectopic calcification of elastic fibers throughout the skin, retina, and arteries. It is caused by pathogenic variants in ABCC6 , which encodes a transmembrane transporter that primarily localizes to hepatocytes. Loss of ABCC6 function in hepatocytes leads to systemic deficiency of inorganic pyrophosphate (PPi), a potent inhibitor of calcification; such depletion of PPi from the circulation is responsible for multisystemic ectopic calcification seen in PXE. Therefore, liver-targeted variant correction by genome editing and subsequent restoration of systemic PPi may offer a one-and-done therapeutic approach for PXE. The ABCC6 …
Using The Safety Scissors: Dna Resection Regulation At Dna Double-Strand Breaks And Telomeres, Michael M, Soniat, Logan R. Myler
Using The Safety Scissors: Dna Resection Regulation At Dna Double-Strand Breaks And Telomeres, Michael M, Soniat, Logan R. Myler
Department of Biochemistry and Molecular Biology Faculty Papers
DNA resection is a universal process in genome maintenance by which one strand of DNA is degraded, leaving the other strand intact. This sometimes highly processive process is critical for many forms of DNA damage repair, replication-coupled repair, meiotic recombination, and telomere maintenance. Therefore, resection must be tightly regulated to prevent genome instability and promote faithful and accurate repair. Here, we review what is known about how resection functions and how it is controlled, using DNA double-strand break repair and telomere maintenance as examples. We address how resection is regulated in three independent steps: resection initiation, long-range processing, and termination. …
Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou
Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and …
A Kinetic Model For Compound Heterozygous Pathogenic Variants In Tyrosyl-Trna Synthetase Gene Yars2-Associated Neonatal Phenotype, Thomas W Christian, Sunita Maharjan, Sitao Yin, Yuka Yamaki, Isao Masuda, Fenglin Li, Colleen Muraresku, Sheila Clever, Rebecca Ganetzky, Ya-Ming Hou
A Kinetic Model For Compound Heterozygous Pathogenic Variants In Tyrosyl-Trna Synthetase Gene Yars2-Associated Neonatal Phenotype, Thomas W Christian, Sunita Maharjan, Sitao Yin, Yuka Yamaki, Isao Masuda, Fenglin Li, Colleen Muraresku, Sheila Clever, Rebecca Ganetzky, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Human genetic disorders are often caused by mutations of compound heterozygosity, where each allele of the mutant gene harbors a different genetic lesion. However, studies of such mutations are hampered due to the lack of an appropriate model. Here we describe a kinetic model of compound heterozygous variants in an obligate enzyme dimer that contains one mutation in one monomer and the other mutation in the second monomer. This enzyme is encoded by human YARS2 for mitochondrial tyrosyl-tRNA synthetase (mt-TyrRS), which aminoacylates tyrosine to mt-tRNATyr. YARS2 is a member of the genes for mt-aminoacyl-tRNA synthetases, where pathogenic mutations …
Stem-Loop And Circle-Loop Tads Generated By Directional Pairing Of Boundary Elements Have Distinct Physical And Regulatory Properties, Wenfan Ke, Miki Fujioka, Paul Schedl, James Jaynes
Stem-Loop And Circle-Loop Tads Generated By Directional Pairing Of Boundary Elements Have Distinct Physical And Regulatory Properties, Wenfan Ke, Miki Fujioka, Paul Schedl, James Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
The chromosomes in multicellular eukaryotes are organized into a series of topologically independent loops called TADs. In flies, TADs are formed by physical interactions between neighboring boundaries. Fly boundaries exhibit distinct partner preferences, and pairing interactions between boundaries are typically orientation-dependent. Pairing can be head-to-tail or head-to-head. The former generates a stem-loop TAD, while the latter gives a circle-loop TAD. The TAD that encompasses the Drosophila even skipped (eve) gene is formed by the head-to-tail pairing of the nhomie and homie boundaries. To explore the relationship between loop topology and the physical and regulatory landscape, we flanked the nhomie boundary …
A Trna Modification Pattern That Facilitates Interpretation Of The Genetic Code, Isao Masuda, Ya-Ming Hou
A Trna Modification Pattern That Facilitates Interpretation Of The Genetic Code, Isao Masuda, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
Interpretation of the genetic code from triplets of nucleotides to amino acids is fundamental to life. This interpretation is achieved by cellular tRNAs, each reading a triplet codon through its complementary anticodon (positions 34–36) while delivering the amino acid charged to its 3′-end. This amino acid is then incorporated into the growing polypeptide chain during protein synthesis on the ribosome. The quality and versatility of the interpretation is ensured not only by the codon-anticodon pairing, but also by the post-transcriptional modifications at positions 34 and 37 of each tRNA, corresponding to the wobble nucleotide at the first position of the …
Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima
Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima
Department of Biochemistry and Molecular Biology Faculty Papers
The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …